The goal of the Colorado Lung Cancer SPORE is to conduct translational research studies that will lead to a reduction in lung cancer deaths through improved early detection, prevention, and treatment. The Colorado Lung Cancer SPORE has 4 scientific projects that are designed to elucidate the role of altered signal pathways and genetic changes that are involved in the pathogenesis and progression of lung cancer and to use these alterations as biomarkers for risk, for early detection, and for developing new chemoprevention and treatment strategies. Project 1 is conducted by Drs. Drabkin, Gemmill, and Chan and studies the role of SemaSF as a tumor suppressor gene. New treatment strategies are evaluated in lung cancers with a Sema signature. Project 1 investigators also evaluate control of the epithelial to mesenchymal transition by the Slug/Snail/Zeb family of transcriptional repressers and ways to reverse the transition in order to reduce metastases and increase sensitivity to lung cancer therapies. Project 2 is conducted by Drs. Bunn, Chan, Heasley, and Hirsch and examines the role of autocrine growth factors (EGFR, BK2R, FGFR, IGF-1R) pathways in lung cancer. Specific pathway inhibitors are evaluated as are biomarkers of sensitivity for these inhibitors. Project 3 is conducted by Drs. Nemenoff, Geraci, Keith, Winn, Meyer, and Merrick and is evaluating the role of prostacyclin and PPARy in lung cancer. Specific agonists are evaluated for their effects on lung cancer prevention and growth. Project 4 investigators (Drs. Miller, Byers, Varella-Garcia, Hirsch, and Duncan) are discovering and evaluating biomarkers of lung cancer risk, biomarkers of chemoprevention effects and evaluating new chemoprevention strategies. There are 4 shared core resources: 1) The tissue bank and biomarkers core (Drs. Franklin, Hirsch, Merrick, and Varella Garcia); 2) The clinical Trials core (Dr. Keith); 3) The Biostatistics / Informatics core (Drs. Baron and Ms. Bondy); and 4) The Administration core (Drs. Bunn and Miller, and Ms. Berrier). Our prior success can be documented by their basis for a large number of ongoing trials including the use of FISH and serum proteomic profiles for patient selection for EGFR inhibitors, the use of iloprost and rosiglitazone for chemoprevention, the use of histology and ASD as intermediate biomarkers for chemoprevention, the use of HDAC inhibitors to increase sensitivity to EGFR TKIs, the use of methylation markers and aneusomy for early detection and the use of CU201 as a new therapy. Our cohort population and tissue banks provide materials for studies within our SPORE, with other SPOREs, and with other national efforts such as SWOG, EDRN SPECS, and LCBCC.